This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cytomegalovirus (CMV) is an important cause of morbidity and occasional mortality in congenitally infected infants and immunocompromised children and adults, especially human immunodeficiency virus (HIV)-infected individuals and transplant recipients. Newborn infants represent a particularly high-risk group as well. CMV vaccine in an adolescent population could ultimately improve pregnancy outcomes, even if it does not prevent infection per se. The main objective is to assess whether injection with 3 doses of the CMV gB/MF59 vaccine will reduce the acquisition of a systemic CMV infection in healthy CMV-seronegative adolescent females. Approximately 2400 healthy females age 12 to 17 years (at time of initial enrollment) will be enrolled into the first part in order to obtain 350 CMV-seronegative subjects for the vaccine trial. Subjects will receive 3 doses of vaccine or saline placebo administered by IM injection in the deltoid muscle on a 0-, 1-, and 6-month schedule. The most important reason for developing a CMV vaccine is to prevent congenital CMV disease. One strategy for the prevention of congenital CMV would be to immunize adolescent girls, or perhaps both boys and girls, before the onset of sexual activity as sexually activity is clearly an important mode of transmission after infancy and the toddler years. The trial is designed to examine the vaccine in a likely target population for a CMV vaccine.